Cancer Clinical Trial
Official title:
Incidence, Clinical Management and Molecular Factors Associated With the Development of Immune-related Adverse Events in Cancer Patients Receiving PD-1 and PD-L1 Inhibitors: a Prospective Observational Study
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti- PD-L1 (atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological guidelines. Durable responses and prolongation of survival with these agents come at the price of the development of immune related adverse events (irAEs). Innovative tools are required in order to manage irAEs and to prevent their potential relapse, with the goal to improve the outcome of patients. In this regard, the Investigators aim to develop a multidisciplinary clinical pathway for cancer patients that are treated with immune checkpoint inhibitors.
Recent evidences in immuno-oncology showed an important role of the immune system in tumor
control. In fact, immune response, both innate and adaptive one, is the first defensive
mechanism against cancer. However, several tumors, during their progression, develop an
immune-tolerance characterized by the activation of immune inhibitory pathways including PD-1
and PD-L1.
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti-PD-L1
(atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological
guidelines.
Currently, the aforementioned agents are approved for the treatment of advanced malignant
melanoma; non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) and the number of
treatment indications for immune checkpoint inhibitors is expanding. Durable responses and
prolongation of survival with these agents come at the price of the development of
immune-related adverse events (irAEs).
Immune-related adverse events are due to the loss of immune-tolerance towards structures of
the self, with the induction of chronic inflammation with an autoimmune mechanism that can
involve numerous organs and systems. The most frequent irAEs reported in clinical trials are
represented by skin toxicity, gastrointestinal toxicity, endocrine toxicity, pulmonary
toxicity, and others such as polymyalgia rheumatica, polyarthritis, myositis, nephritis,
polyradiculoneuritis, encephalitis and myocarditis.
The irAEs reported in clinical trials with nivolumab amount to a maximum of 85% considering
all grade of toxicities, while approximately 75% of patients treated with pembrolizumab
presented irAEs. Grade 3/4 irAEs were reported in 10% of patients treated with anti-PD-1.
With atezolizumab fewer patients had treatment-related grade 3 or 4 adverse events (15%).
In most cases, irAEs occur within some weeks after starting of immunotherapy; however these
toxicities have been reported later and also years after treatment discontinuation. The
development of irAEs is associated with significant morbidity and mortality in cancer
patients treated with immune checkpoint inhibitors, and therefore they may significantly
affect the quality of life, even in patients achieve the control of neoplastic disease.
The overseeing, early diagnosis and clinical management of immune checkpoint inhibitors'
toxicities in the clinical setting are, currently, not standardized.
Innovative tools are required in order to manage irAEs and to prevent their potential
relapse, with the goal to improve the outcome and quality of life of these patients.
In this regard, the Investigators also aim to evaluate a model of multidisciplinary clinical
pathway for cancer patients that are treated with immune checkpoint inhibitors in order to
improve their management and also ameliorate the quality of life of patients that develop
irAEs.
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